1. Field of the Invention
The present invention relates to methods and apparatus for detecting one or more ligands in candidate substances. More specifically, the invention is directed to methods and apparatus using biosensors incorporating G-Protein Coupled Receptors (GPCRs) for detecting specific substances or ligands, or for detecting specific objects or people associated with specific substances or ligands.
2. Description of Related Art
Biosensors have been in use for more than 30 years. In the past 7 to 8 years, however, the rate of development of biosensor technology has rapidly increased.
Biosensors are composed of a biological sensing element in intimate contact with some form of a physical transducer. Together, these two elements relate the concentration of a target analyte or ligand with some measurable signal. The earliest biosensors were simply enzymes immobilized on solid surfaces of oxygen electrodes which measured the consumption of oxygen in response to the enzymatic breakdown of substrate.
Enzyme-based biosensors have found their greatest use in the medical field for body fluid analyses (e.g. urine sugar content, blood sugar levels, serum cholesterol, lactate, and acetylcholine). Recently, a variety of other oxidative and reductive enzymes have been immobilized and coupled to colorimetric changes in product or to potentiometric or electrochemical changes in response to enzyme activities. These enzyme-based systems have been used most extensively for environmental monitoring (contaminants, pesticides, herbicides, and organic solvents) and in some cases for process stream monitoring. The sensors are suitable for multiple use and continuous monitoring up to certain limits. In general, end-product build-up leads to inhibition of the enzymatic activity, enzyme inactivation can occur as well as enzyme degradation all of which can lead to deterioration of the sensor function. Typical sensor lifetimes are only a few days.
Two additional types of biosensors have been recently developed and field-evaluated. One type exploits the highly selective recognition between antibodies and their antigens, while the second type exploits whole bacterial cells that report the presence of the target ligand through the production of light, or through a change in metabolic function.
An antibody sensor in an advanced state of development is that developed by the Naval Research Laboratory by Ligler (Naval Research Reviews, vol. 14, 1994). These biosensors use either monoclonal antibodies, which recognize a single epitope or site on the antigen or polyclonal antibodies, which recognize many epitopes on the antigen. The NRL biosensor can exploit two different types of immunological assay conditions. The response times for antibody sensors are in the range of minutes and sensitivities are nanograms per liter.
In one case, a sandwich immunological assay is used. In this assay type, antibodies for the target analyte or ligand are immobilized on an optical fiber. A solution containing the same antibodies which are labeled with a fluorophore is added with the experimental sample of ligand. The ligand binds to both sets of antibodies creating links between the immobilized antibodies on the fiber and the labeled antibodies. Thus the antigen is xe2x80x98sandwichedxe2x80x99 between the immobilized antibodies on the fiber and the labeled antibodies. The excitation of the fluorophore occurs through the fiber and only those fluorophores in very close proximity (ca. 150 nm) to the fiber (those bound in the sandwich) create an optical field on the surface of the fiber called the evanescent wave. This is the signal that is measured and it is proportional to the amount of ligand (and, consequently, fluorophore) bound to the fiber.
This type of antibody sensor requires sufficiently large antigens on the order of the size of small peptides (10,000 Daltons) to the size of large proteins (hundreds of thousands of Daltons), bacterial spores or viruses to ensure that a xe2x80x98sandwichxe2x80x99 is generated.
The second type of antibody sensor is based upon the competition between fluorescently labeled antigen and unlabeled antigen for binding sites on the fiber-immobilized antibodies. The same basic sensor design is used. The measurement is based on the reduction in fluorescence on the fiber due to binding of the unlabeled ligand which competes for sites where the labeled antigen was present in the initial calibration. The competitive immunoassay is highly suitable for small molecular species (e.g. less than 2000 Daltons). Other types of antibody sensors have been developed that exploit a variety of optical transduction schemes, including, resonance energy transfer between the chromophore bound on the antibody, which then transfers energy to chromophores bound to the ligand.
Cell-based sensors have also been developed. Among the most common to date, are genetically transformed bacterial cells are used in which the genes for bioluminescence (bacterial genes for bioluminescence are called lux genes) have been inserted to provide a means of reporting, through the generation of light, the presence of an analyte that is xe2x80x98recognizedxe2x80x99 by the bacteria. For example, bacteria that possess the genes to bind intracellular copper (Cu++) were transformed to possess the lux genes as well. When Cu++ enters the cell, the genes encoding the copper-binding proteins are xe2x80x98turned onxe2x80x99 or expressed. Concomitant with the activation of the genes for Cu++ binding is expression of the lux or light-producing genes. This coupling of gene expression for these two different functions is achieved by placing the lux genes under the influence of the promoter of the genes encoding the Cu++ binding proteins. Consequently, when the cells take up Cu++, they generate light thereby reporting the presence of intracellular Cu++. The light emission can be detected with a CCD (Charged Coupled Device) camera, or if the cells are immobilized either on a fiber optic or a surface, the light production can be quantified using a CCD chip.
Since Cu++ is the bioactive form of copper, the cell reports and can quantify the bioavailable copper in a sample making this biosensor more useful for many ecological and environmental studies than analytical techniques that quantify total copper. The current sensitivity of the copper biosensor is in the micromole range. In a similar fashion, investigators have linked lux genes to genes encoding degrading enzymes for a variety of organic toxicants such as naphalene and toluene and have achieved nano- to picomole sensitivities in cell-based sensors with high specificity.
Because these systems require gene expression in response to the presence of a target ligand to report the presence of the ligand, they do not possess rapid response timesxe2x80x94generally 15-30 minutes for a detectable response and 60 minutes for maximal light production. However, they can be used remotely and can have significantly long operational lifetimes. More recently, bacterial metabolic functions have been exploited as biosensors. Intracellular degradation or conversion of target ligands are xe2x80x9creportedxe2x80x9d through the electrochemical detection of intermediates or end-products that are suitable for detection modes when the target ligand is not. Lastly, bacterial cell biosensors have been generated by the expression of non-endogenous enzymes on the cell surface that convert target ligands that are not normally taken up by the cells into chemical species that can be readily metabolized and reported as described above.
Tissue and organ based biosensors have also been developed. These often exploit insect antennae or excitatory tissues (neurons). Such biosensors are often coupled to electrical transduction and recording schemes. A major shortcoming to these technologies is the short (generally hours) operational lifetimes of the tissues or organs in the biosensor format.
The current technologies for ligand or substance detection in the vapor or aqueous phase of the environment and in medical or biological fluids of clinical subjects are generally costly, time-consuming and are, for the most part, not portable nor are they suitable for stand-alone, long-term surveillance or monitoring applications. There is a need for biologically based sensor technologies that offer an inexpensive solution to a broad range of ligand or substance detection (e.g. illicit drugs, explosives, environmental toxicants, process stream products or intermediates, chemical and biological warfare agents, and clinically important or relevant ligands) and provide long-term, stand-alone utility suitable for vapor- and/or liquid-phase detection modes.
The present invention, which is directed to methods and apparatus comprising GPCR-based biosensors for detecting ligands or substances, is intended to overcome the above-described limitations and deficiencies of currently available biosensors. The GPCR-receptor-based methods and apparatus for detecting specific substances achieve (a) more rapid turn-over timesxe2x80x94in the millisecond time domainxe2x80x94than prior art biosensors, (b) greater ligand or substance range as many ligands of interest are too toxic for the generation of antibodies, other ligand species lack adequate antigenicity (e.g. metal ions, undecorated ring structures, certain small inorganic ion species, certain small organics), or many ligands of interest do not have a known or suitable enzymatic conversion process (due to unavailability of an enzyme, enzyme instability, or prohibitive cost of purification for a biosensor application). Accordingly, objects of the present invention include providing receptor-based biosensors that are less sensitive to interference to poisoning by other ligands which may be present under specific sensing conditions, have broad analyte detection capabilities, have highly selective ligand specificity, have receptors that are not consumed in the detection step and hence fully reversible, and have receptors that are stabilized for biosensor applications at low costs, and, in certain aspects, provide receptors in sensing elements that are highly tolerant of toxicants, including organic solvents.
The methods and apparatus provided by the present invention for detecting ligands or substances are advantageous due to their high sensitivity, rapid response time, high selectivity for single ligand or ligand class, high signal to noise ratio, self-calibrating capability, field portability and remote field applications, broad range of interrogatable systems (liquids, vapors), extended lifetimes of apparatus and stand alone use, cost-effectiveness and durability.
In one aspect, the present invention is directed to a method for detecting a ligand in vapor phase. The method involves providing a sensing element which comprises a GPCR having preferential specificity for the ligand. The sensing element includes immobilized transformed eucaryotic cells heterologously expressing the GPCR, with the proviso that the eucaryotic cell line cannot be frog melanophore cells. In one aspect, the sensing element includes a fluorescing element that is selectively responsive to binding of the ligand to the GPCR. A preferred line of cells for use in the sensing element is a fungal cell line, in particular, a yeast cell line. A vapor phase or liquid phase specimen which contains a candidate substance is obtained, and the sensing element is exposed to the vapor- or liquid-phase specimen. The method further involves monitoring the response of the sensing element, and comparing the response with a previously established response for the ligand. A preferred form of monitoring comprises automatic optical detection of a change in optical characteristics of the sensing element.
The invention provides an apparatus for detecting a ligand in vapor- or liquid-phase. The apparatus comprises a sensing element which comprises a GPCR, means for exposing a candidate substance to the sensing element, and means for monitoring response of the sensing element. For example, a typical class of GPCRs which are adapted for use in the apparatus are Adrenoceptor GPCRs, mutants of which can be selected and incorporated into the apparatus or method of the invention for detecting explosives, like TNT because these GPCRs recognize small organics with aromatic rings.
The apparatus may comprise one or more different GPCRs. In one embodiment, the monitoring means comprises automatic optical means for detecting a change in optical characteristics of the sensing element. An embodiment of the apparatus"" exposing means involves means for directing a vapor-phase specimen of the candidate substance to the sensing element. Another embodiment of the appartus"" exposing means involves means for directing a liquid-phase specimen of the candidate substance to the sensing element. The apparatus may further comprise means for comparing the response with a previously established response for the ligand and still further means for reporting that comparison electronically, optically or audibly. The apparatus may still further comprise utilization means which are responsive to the comparing means and for providing an appropriate action. The utilization means are selected from the group consisting of an annunciator for alerting an operator to results of the comparison; a door lock or other automatic access-control device for admitting or not admitting a person to a facility; a lock or other automatic access-control device for enabling or not enabling a person to have access to use of a facility, an apparatus, credit, information, a service or other data bases; and an automatic transport device for carrying or not carrying an object through or into a facility or apparatus.
Another important aspect of the invention is directed to a method of detecting a specific substance which method involves the step of providing a GPCR that is specifically responsive to the specific substance. Suitable GPCRs are obtained from GPCRs well known in the art for their ligand specificity, or GPCRs are provided by conducting mutagenesis and selection on a known sequence of nucleotides encoding a GPCR, for example the sequence encoding Adrenoceptors GPCR or any other GPCR sequence, and selecting a sequence of nucleotides for a GPCR having preferential specificity for the specific substance. The GPCR(s), incorporated into a sensing element, are caused to be exposed to a candidate substance. In a preferred embodiment, transformed eucaryotic cells, in particular, yeast cells heterologously expressing a GPCR, are immobilized and incorporated into the sensing element. In one aspect, the sensing element further comprises a fluorescing element incorporated into the cells and which produces an response upon binding of a ligand of interest by the GPCR. The eucaryotic cells cannot be frog melanophore cells.
The GPCRs provided in the method of the invention are obtained by conducting mutagenesis and selection for GPCRs that are preferentially responsive to a specific substance. Examples of such substances include, but are not restricted to, an explosive and a narcotice or substances structurally or behaviorally related to an explosive or a narcotic. Examples of the explosive and narcotic include TNT and cocaine, respectively.
An apparatus is provided by the invention for detecting a specific substance. The apparatus comprises a GPCR, provided either from a GPCR of known specificity or derived by mutagenesis and selection and which is preferentially responsive to the specific substance. The GPCR is incorporated into a sensing element. The apparatus comprises means for exposing a candidate substance to the GPCR, and means for monitoring the response of the GPCR to the candidate substance. Embodiments of the apparatus comprises monitoring means for automatic detection of a change in optical characteristics of the sensing element. Still further embodiments of the apparatus include utilization means as described above.
In yet another aspect, the invention is directed to a method for detecting specific objects or people possessing, contaminated or otherwise associated with specific substances such as but not restricted to TNT or illicit drugs. The method involves exposing an object or person to a sensing element that includes a GPCR specific for the ligand of interest, monitoring the response of the GPCR, and comparing the response with a previously established response for a specific object or person. In the exposing step, the method includes exposing the object or person to a GPCR, and a preferred embodiment involves exposing the object or person to transformed eucaryotic cells heterologously expressing a GPCR, the cells being incorporated into the sensing element. Alternatively, the person or object is exposed to an array of GPCRs or an array of transformed eucaryotic cells with GPCRs having various sensitivities in the sensing element. With an array of GPCRs, the monitoring step is achieved by comparing a pattern of responses from the array with a previously established pattern of responses for a specific object or person. As above, the monitoring step includes automatic detection of a change in optical characteristics of the sensing element. Where the sensing element includes transformed eucaryotic cells, the monitoring step includes automatic detection of a change in optical properties (e.g., chromophore activated fluorescence) of the transformed cells.
The invention provides an apparatus for detecting specific objects or people, the apparatus comprising a sensing element that includes a GPCR, means for exposing an object or person to the sensing element, and automatic monitoring means connected to receive a response from the GPCR. A typical embodiment involves a transformed eucaryotic cells heterologously expressing a GPCR with specificity for the object or person with said substance which is incorporated into the sensing element. An embodiment of the apparatus includes utilization means.
In yet another aspect, the invention provides a method for detecting a ligand, the method comprising the steps of exposing a candidate substance to a sensing element which includes a GPCR, monitoring response of the GPCR, and comparing the response with a previously established response for the ligand. An embodiment of the exposing step includes exposing the candidate substance to a sensing element which includes one or more different GPCRs. The method, which finds particular use in detecting a specific substance that includes the ligand, is directed alternatively to exposing a candidate substance to an array of the GPCRs having various different sensitivities, followed by a monitoring step which includes comparing a pattern of responses from the array with a previously established pattern of responses for the specific substance. As above, the GPCR can be derived from mutagenesis of a known sequence encoding a known GPCR and selection of a GPCR having a preferred specificity and sensitivity to the ligand or the specific substance that includes the ligand. The exposure step may involve obtaining a vapor or liquid phase specimen of the candidate substance and directing this specimen to the sensing element. The monitoring step can be either automatic optical detection of a change in optical characteristics of the sensing element, or automatic electronic detection of a change in electrical characteristics of the sensing element. Involvement of optical detection includes automatic optical detection of a conformationally amplified or induced change in fluorescence of the sensing element.
The apparatus for detecting a ligand comprises a sensing element which includes a GPCR, means for exposing a candidate substance to the sensing element, and means for monitoring response of the GPCR. As above, the sensing element may include one or more different GPCRs. In a typical embodiment, the GPCR is coupled with a chromophore and when responding to the ligand undergoes a conformationally induced change in fluorescence. The apparatus finds particular use in detecting a specific substance that includes the ligand, and the sensing element can include an array of GPCRs having various different sensitivities, and monitoring means that include means for comparing a pattern of responses from the array with a previously established pattern of responses for the specific substance. The GPCRs can be selected from GPCRs of known specificity or can be obtained by mutagenesis from a known or derived GPCR, and selection of GPCR fragments having the desired specificity and sensitivity to a ligand or specific substance of interest. Embodiments of the apparatus include monitoring means selected from the group consisting of automatic optical means for detecting a change in optical characteristics of the sensing element, and automatic electronic means for detecting a change in electrical characteristics of the sensing element.
A further embodiment of the apparatus includes means for directing a vapor- or liquid-phase specimen of a candidate substance to the sensing element. The apparatus further comprises means for comparing the response with a previously established response for the ligand. In yet another embodiment, the apparatus further comprises, as above, utilization means which are responsive to the comparing means, for providing an appropriate action. The utilization means are selected from the group consisting of an annunciator for alerting an operator to results of the comparison, a door lock or other automatic access-control device for admitting or not admitting a person to a facility, a lock or other automatic access-control device for enabling or not enabling a person to have access to use of a facility, an apparatus, credit, information, or a service, and an automatic transport device for carrying or not carrying an object through or into a facility or apparatus.
The present invention is further directed to a method of detecting specific substances including, but not limited to, chemical warfare agents, biological warfare agents, toxic agents, narcotics, pharmaceuticals, explosives, process stream analytes, impurities, waste materials, environmental pollutants, and clinically relevant ligands, typically, metabolites, hormones, electrolytes, nitric oxide, and proteins. The method comprises providing a coding sequence for a GPCR having a known specificity that is preferentially responsive to a specific substance selected from the group enumerated above. Another step of the method involves causing the GPCR, which is incorporated into a sensing element, to be exposed to a candidate substance. In preferred embodiments, the causing step includes at least one substep selected from the group consisting of incorporating the GPCR into a sensing element, shipping the GPCR to a person for use in screening for the specific substance, and providing instructions for use of the GPCR in screening for the specific substance.
The invention provides an apparatus for detecting any one of specific substances selected from the group consisting of chemical warfare agents, biological warfare agents, toxic agents, narcotics, pharmaceuticals, explosives, process stream analytes, impurities, waste materials, environmental pollutants, and clinically relevant ligands. The apparatus comprises a GPCR that is preferentially responsive to a specific substance selected from the group enumerated above. The apparatus also comprises means for exposing a candidate substance to the GPCR, and means for monitoring the response of the GPCR to the candidate substance.
In yet another aspect, the invention is directed to a method of detecting a specific substance, the method involving the step of providing a GPCR preferentially responsive to the specific substance. The GPCR is situated in a host structure selected from the group consisting of eucaryotic cells, a synthetic membrane system, and a synthetic polymer system. Another step of the method involves causing the host structure in which the GPCR is situated to be exposed to a candidate substance.
Accordingly, the invention provides apparatus for detecting a specific substance, the apparatus comprising a GPCR that is preferentially responsive to a specific substance and situated in a host structure selected from the group consisting of eucaryotic cells, a synthetic membrane system and a synthetic polymer system. The apparatus also comprises means for exposing a candidate substance to the host structure in which the GPCR is situated. The cell host structure of the apparatus is selected from the group consisting of eucaryotic cells. Typical synthetic membrane systems which find use in the invention are liposomes, other combinations of lipids, detergents, fatty acids and proteins that will form membrane-like vesicles. Typical synthetic polymer systems include but are not restricted to conducting organic polymers derived from aromatic or heteroaromatic materials e.g. polypyrrole, methyl pyrrole, poly(5-carboyindole).
Another aspect of the invention is directed to a method of detecting a specific substance which involves the step of manufacturing a biosensor that includes eucaryotic cells physically suspended on or in a hydrogel or other supporting material which serves to immobilize the cells and provide nourishment from material held within the hydrogel. Another step involves causing the cells to be exposed to a candidate substance.
A preferred embodiment of the method involves selecting transformed cells that heterologously express a GPCR which is preferentially responsive to the specific substance. The method further comprises the steps of monitoring response of the cells to the candidate substance, and the step of comparing the response with a previously established response for the specific substance. The monitoring step preferably includes automatic detection of a change in optical or electrical characteristics of the cells.
In another aspect, the method of detecting a specific substance involves the step of manufacturing a biosensor that includes one or more GPCR""s having preferential ligand specificity and mounted in a synthetic polymer or synthetic membrane. The method further comprises the steps of monitoring response of the synthetic membrane or polymer to the candidate substance, and the step of comparing the response with a previously established response for the specific substance. The monitoring step preferably includes automatic detection of a change in optical or electrical characteristics of the synthetic membrane or polymer.
A further aspect of the invention is directed to a method of making a biosensor for detecting a specific substance. The method comprises the steps of providing transformed cells which heterologously express a GPCR preferentially responsive to the specific substance; providing an immobilizing medium typically as a hydrogel; providing nourishment within the hydrogel for the cells; suspending the cells on or in the hydrogel to draw nourishment from material held within the hydrogel; and incorporating the hydrogel, with the cells and nourishment, into a carrier for exposure to a candidate substance. The cells for use in the method heterologously express a GPCR that is preferentially responsive to the specific substance. A further step involves functionally interconnecting the carrier with means for monitoring response of the GPCR to the candidate substance.
An apparatus made by this method is provided by the invention.
In another aspect, the method of making a biosensor for detecting a specific substance is directed the step of manufacturing a biosensor that includes one or more GPCR""s having preferential ligand specificity and mounted in a synthetic polymer or synthetic membrane. The method further comprises the steps of monitoring response of the synthetic membrane or polymer to the candidate substance, and the step of comparing the response with a previously established response for the specific substance. The monitoring step preferably includes automatic detection of a change in optical or electrical characteristics of the synthetic membrane or polymer. An apparatus made by this method is provided by the invention
In particular, the invention provides an apparatus for detecting a specific substance, the apparatus comprising a sensor that includes a nourishing hydrogel serving to immobilize and nourish transformed eucaryotic cells that heterologously express a GPCR which is preferentially responsive to a specific substance. The apparatus also comprises means, responsive to a characteristic of the cells, for deriving a signal related to presence or absence of the specific substance. Also provided are means for exposing a candidate substance to the sensor. As above, a preferred embodiment of the cells are transformed cells which heterologously express a GPCR which is preferentially responsive to the specific substance. The signal-deriving means typically comprises means for monitoring the response of the GPCR to the candidate substance. The monitoring means typically includes means for automatic detection of a change in optical or electrical characteristics of the cells.
A preferred embodiment of the apparatus in which the signal-deriving means comprise means for monitoring the response of the GPCR to the candidate substances involves a further combination with automatic means for comparing the change in characteristics with a change in the same characteristics in presence of the specific substance. This further combination also involves utilization means, responsive to the automatic comparing means. The utilization means are selected from the group consisting of an annunciator for alerting an operator to results of automatic comparison, a door lock or other automatic access-control device for admitting or not admitting a person to a facility, a lock or other automatic access-control device for enabling or not enabling a person to have access to use of a facility, an apparatus, credit, information, or a service, and an automatic transport device for carrying or not carrying an object through or into a facility or apparatus.
Yet another aspect of the invention is directed to a method of detecting a specific substance, the method comprising the step of manufacturing a biosensor that includes a GPCR which is preferentially responsive to the specific substance. The GPCR comprises or incorporates a signaling element selected from the group consisting of a chromophore for responding to a substance by fluorescing, and an electrical mechanism for responding to a substance by a change in an electrical property. The GPCR also has incorporated a conformational response for inducing the signaling, in comparison with a background signal level. The method also involves causing the biosensor to be exposed to a candidate substance. Further comprising steps of the method are monitoring response of the biosensor to the candidate substance, and the step of comparing the response with a previously established response for the specific substance. Preferably, the monitoring step includes automatic detection of a change in optical or electrical characteristics of the biosensor.
The invention in another aspect is directed to a method of making a GPCR for use in a biosensor to detect a specific substance. The method comprises the steps of providing a GPCR that has a preferential response to the specific substance. The method involves the step of incorporating into said GPCR a signaling element selected from the group consisting of a chromophore for responding to a substance by fluorescencing, and an electrical mechanism for responding to a substance by a change in an electrical property. Another step is directed to incorporating into said GPCR a conformational response for inducing the signaling, in comparison with a background signal level.
Another aspect of the invention is directed to a GPCR made by the above method.
The invention is further directed to an apparatus for detecting a specific substance, in which the apparatus comprises a biosensor that includes a GPCR preferentially responsive to the specific substance and which incorporates a signaling element selected from the group consisting of a chromophore for responding to a substance by fluorescing, and an electrical mechanism for responding to a substance by a change in an electrical property. Also, the GPCR incorporates a conformational response for inducing the signaling, in comparison with a background signal level. The apparatus also includes means for exposing the biosensor to a candidate substance.
In another aspect, the invention is directed to an apparatus for detecting a specific substance, the apparatus comprising at least one biosensor that includes a GPCR which is preferentially responsive to the specific substance. The apparatus also comprises means for exposing the biosensor to a candidate substance, means for monitoring the GPCR response, and at least one independent, demountable cartridge for holding the biosensor and for use by an operator in selectively disposing the biosensor in position relative to the exposing means and the monitoring means for detection, or removing the biosensor from position for detection. In one embodiment, the biosensor of the apparatus includes a host structure which encompasses the GPCR, and the cartridge also includes resources for maintaining the host structure, with the GPCR in operable condition. A typical host structure includes transformed eucaryotic cell which heterologously express GPCR, the cells deriving nutrition from resources included in the cartridge that comprise nutriments for sustenance of the cells. A version of the apparatus is directed to one in which the cartridge is for disposal or replenishment when the nutriments are exhausted or the cell viability has declined. Another embodiment of the apparatus further comprises a multiplicity of GPCRs representing different types, respectively, preferentially responsive to a corresponding multiplicity of respective different specific substances. In this embodiment, there is a corresponding multiplicity of cartridges, respectively holding different ones of the GPCRs, the cartridges being substantially interchangeable. Accordingly, with a multiplicity of GPCRs and the correspondingly multiplicity of cartridges, the apparatus is efficiently usable by an operator for detecting selectively any of the multiplicity of specific substances.
The above-discussed and many other features and attendant advantages of the present invention will become better understood by reference to the following detailed description of the invention taken in conjunction with the accompanying drawings.